Research to combat dual epidemics: A conversation with CDC’s Jordan Tappero

Science Speaks is delving into the global HIV and tuberculosis research and development efforts at the U.S. Centers for Disease Control and Prevention (CDC) with a series of interviews with staffers who are key to the success of their programs. For the fourth interview in the series, we spoke with Jordan W. Tappero, MD, MPH, who is currently serving as director for the Health Systems Reconstruction Office in the Center for Global Health, an office opened in response to the January 2010 earthquake in Haiti. Dr. Tappero describes his early research in HIV and TB, thoughts on why Uganda is the only sub-Saharan African country not enjoying a reduction in HIV incidence, and how quickly HIV services were restored to people living in Haiti after the January 2010 earthquake.

What got you interested in working in public health?Immediately following my internal medicine residency training, I spent a year working as a volunteer physician in a Cambodian refugee camp hospital on the Thai-Cambodian border. About 2 million Cambodian refugees were along the border after the Vietnam conflict. There I took care of a lot of the young children, and learned the value of thinking about prevention of disease, as well as the treatment and care side.

I returned from the border to the San Francisco Bay Area in 1987, right at the peak of AIDS epidemic, in the era that preceded effective antiretroviral drug treatment. I came to San Francisco because I got very interested in looking at Kaposi’s sarcoma [a common cancer found in AIDS patients] and other cutaneous diseases in AIDS patients as a research question. While working at the University of California, San Francisco (UCSF), I also obtained a master’s in public health from UC Berkeley. While seeing AIDS patients in the clinic, we stumbled upon a skin disease that looked something like Kaposi’s sarcoma, and that had been given the name bacillary angiomatosis. In short, the tools I had acquired at UCSF and at UC-Berkeley allowed us to identify the causative bacterial agents of bacillary angiomatosis, their principal animal reservoirs and insect vectors, and shed corrective light on the cause of “cat scratch disease” in children. After making some real contributions with Bartonella species infections, I moved to the CDC to further pursue a career in public health epidemiology.

Tell me about the field research you did in Botswana on HIV and tuberculosis (TB). What do the HIV and TB epidemics look like there now?I started out at CDC as an officer in the Epidemic Intelligence Service, and when I completed my field training in July 1995, I took a job opening the CDC’s overseas field station in Botswana. Reason being, Botswana had the highest HIV prevalence in the world at that time, with 38 percent of adults infected between the ages of 15 and 45. The Botswana National TB Program that had improved so much in the 1960s and ‘70s was suddenly seeing this huge upsurge in active disease. I went there to try and learn what we could about improving TB control in high-HIV prevalence countries. We were really at the very beginning of seeing the explosion of HIV-associated TB in sub-Saharan Africa. When you’re infected with Mycobacterium tuberculosis you have a 10 percent lifetime risk of developing the disease. When HIV is introduced into the picture, the risk of developing active TB becomes 10 percent per year.

We tried to understand what we now know, that HIV infected patients are less likely to test sputum smear positive for TB, which means it’s harder to establish a confirmatory diagnosis of TB in people living with HIV. We were finding that among hospitalized adult TB patients, more than 70 percent were HIV-infected. We also looked for other causes of adult respiratory infection in HIV-infected patients, and found only half had TB.

In addition to our concern for adults with difficult to diagnose HIV-associated TB, we were equally concerned about the transmission of M. tuberculosis [or latent] infection among their household contacts – in particular, their children, as the average adult household had an average of six children – that could potentially mean a lot of children at risk for coming down with active TB! So, we were working to understand the role of the tuberculin skin test (TST) to identify recently infected children with M. tuberculosis in this setting. The “dogma” at that time was that the TST could not be used as a screening test for new infection with M. tuberulosis in children in Botswana, because the vast majority of children in Botswana routinely received the Bacillus Calmette-Guérin vaccine (or BCG, a vaccine to prevent acquisition of TB) at birth, and the BCG vaccine would cause a false-positive TST. We wanted to know if this was accurate, as we desperately needed a screening tool to identify children in need of antibiotic prophylaxis against M. tuberculosis.

We showed that the dogma was not true. We conducted a TST survey among more than 800 rural and urban children; all but four had received the BCG vaccine, and 7 percent of all children tested TST positive. TST positive children were significantly more likely to live in a household with a mother or aunt with recently diagnosed active TB.

We were also concerned about HIV-associated TB patients and their response to anti-TB treatment. Keep in mind this was the era before antiretroviral therapy (ART). We were concerned at that time that HIV-infected people, who got very thin and very ill, might not be absorbing their anti-TB meds at their recommended dosage per weight. We found that having low serum concentrations of isoniazid, rifampin and ethambutol (three of four drugs used in the national anti-TB regimen) was not uncommon in these patients.

You worked as the Acting Deputy Director for CDC’s Global AIDS Program, which is part of the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), can you tell me a bit about that experience?I served as CDC Country Director in Thailand for six years beginning in 2000. I took the position for many reasons, but the most compelling was to be CDC’s principal investigator for the world’s first HIV vaccine efficacy trial outside the U.S., a trial conducted in partnership with VaxGen and the Royal Thai Government. We learned a lot from the study – in particular that this high-risk, injection drug using (IDU) population, participated in our study with great follow up and a clear trial endpoint. There was also concern that if IDUs participated in a vaccine trial, their risk behavior (sharing needles, unprotected sex) would increase. We showed that was not true – their risk behavior decreased, in part due to intensive risk reduction counseling. Though the vaccine was shown to have no efficacy, the trial was well-conducted with a very clear endpoint. Moreover, it showed that highly at-risk populations, with effective behavioral counseling, can help us all to learn about the efficacy of new HIV prevention tools in the future.

PEPFAR is a U.S. government program, and the two agencies that contribute most to PEPFAR in terms of programming are CDC and the U.S. Agency for International Development (USAID). PEPFAR came to Thailand in 2002, and was administered by CDC in partnership with the Thai Ministry of Public Health. We partnered to rapidly scale up ART, and demonstrated how to efficiently monitor HIV infected people on treatment in order to improve overall program performance. We also continued to work on prevention research – vaginal microbicides, and evaluation and scale up of prevention of mother-to-child HIV transmission (PMTCT) prophylactic ART regimens among HIV-infected pregnant women as well.

Were you also the CDC Country Director in Uganda?Yes, from 2006 through 2008. In Uganda, CDC contributed to one of the biggest PEPFAR programs in sub Saharan Africa. In the first five years of PEPFAR there were “focus countries” and Uganda was one of them. We were learning to rapidly scale up ART, increase PMTCT coverage in a country where at the time only one-third of women went to the hospital for delivery, and we also looked at the relationship between HIV and malaria. Uganda is a country, especially around Lake Victoria, with very high malaria prevalence.

One of the research questions we were interested in looking at was when to stop giving cotrimoxazole (or Bactrim) antibiotic prophylaxis to children born to HIV-infected mothers. Cotrimoxazole remains to this day, a standard prophylaxis medication for preventing opportunistic infections in HIV-infected children and adults. When a baby is born to an HIV-infected mother, it is not known whether the baby has become HIV-infected until after the cessation of breast feeding. Though PMTCT substantially decreases the risk of HIV transmission, it can still occur during delivery and also through breast feeding. It is well known that a child’s risk of dying during the first six months of life is lowered through breastfeeding due to the immunologic benefits of breast milk. Even if it breast milk can transmit HIV, it is overly beneficial, and it is thus important that these HIV at risk children take cotrimoxazole prophylaxis.

And health care providers have to wait until after breastfeeding is stopped before knowing with certainty the HIV status of the child.

It seems notable and troubling that notwithstanding the early impressive gains made by Uganda in the AIDS response, it is now the only country in sub-Saharan Africa not enjoying reductions in HIV incidence. Why do you think that is the case?I think as more and more people go on ART you will see that new infections will start to drop again in Uganda. Uganda was one of the first African countries to see the HIV epidemic; the incidence and prevalence went up rapidly and prevalence hovered around 18 percent for a long while. Uganda saw benefits from behavioral interventions, PMTCT, and early roll out of ART, and prevalence began to fall. At some point the falling prevalence reached its nadir at around six or seven percent and remained relatively stable there. Now we’re hopeful that this new push around treatment as prevention (for example, the results of the HIV Prevention Trials Network (HPTN) 052 study) will push us again in the direction of decreasing incidence, and over time a declining prevalence as well.

You are now doing work with the Health Systems Reconstruction Office in Haiti. Right after the 2010 earthquake, a lot of schools of medicine set up mobile services clinics for HIV and TB patients to ensure continuation of services. Have these services now been institutionalized again? Do the majority of HIV and TB patients in Haiti have some assurance of access to and continuity of care? There is so much to talk about in Haiti. One of the things we were able to demonstrate and focus on immediately after the earthquake was whether or not the PEPFAR program was being impacted in an extremely negative way by the displacement of 2 million or more people.

There is a publication in press at the journal AIDS which that shows that ART services for those who did not die in the earthquake were restored back to baseline within a couple of months. Within three months, PMTCT coverage was back to pre-earthquake levels and monitoring, counseling and testing was back to its baseline soon thereafter. The first priority was to get HIV-infected patients who were on ART and lost to follow-up back on ART, and to keep them on life-saving treatment.

With more than 2 million people in the Port Au Prince area living in make-shift shelters, we knew that this population was a great risk of acquiring communicable disease, and we had no idea about what the burden of disease was for these conditions even before the earthquake. We knew that with lack of access to clean water and proper sanitation, inadequate care services, and overcrowding, that we needed to rapidly establish a reportable disease surveillance system and coordinate with NGO’s offering clinical care services through syndromic case reporting.

We conducted outbreak investigations when a surge in reporting was seen in order to confirm outbreaks and to prevent them from becoming an epidemic. We knew that in the setting of poor access to clean water and sanitation, we needed to focus on diarrheal disease. Fortunately UNICEF, DINEPA and others were able to establish a way to bring in clean, chlorinated water by trucking daily, allowing displaced persons to take buckets of clean water back to their makeshift shelters. We knew this was where we needed to focus our energy to prevent disease.

We also invested in the ability of the national public health laboratory to confirm causes of these reportable conditions – whether it was malaria, diphtheria, etc. We had to invest in the microbiologic capacity of these labs to do that work, beyond what investments were there for HIV though PEPFAR and the Global Fund already.

Even though it hadn’t been seen there for more than 100 years, a concern for watery diarrhea, including cholera, was included on our list of infections of grave concern. In mid-October there was a cluster of adults that were rapidly tested for cholera and within about 18 hours we had microbiologic confirmation of cholera in Haiti. With that we helped the MOH develop a system to track the spread of cholera, a system that even today is maintained by the Ministry of Health and Population on their public access website. Of note, although the case fatality ratio for cholera was alarmingly high in the first few weeks of the outbreak at five percent, within three months, it fell to below the international goal of one percent or less. Today it is well below half of one percent (or one in 200), a great accomplishment by the Ministry of Health and its partners given the underlying water and sanitation conditions.

To date, more than 550,000 cases of cholera have been reported in Haiti, with more than 7,000 deaths (of note, not all of these cases are culture-confirmed). Though Haiti’s cholera surveillance system is among the best in the world at this time, we know there are still people who don’t make it to a health facility to be reported, and that not all cases reported by the system are in fact cholera.

Now we are working to dramatically improve Haiti’s water and sanitation as a means to combat cholera. One of our biggest efforts was to get people to chlorinate the water that they drink. Only 17 percent of people in Haiti have access to a toilet or latrine (most practice open defecation) which continues to contaminate open water sources such as lakes and streams.

The reality is that as long as access to clean water and improved sanitation remain limited in Haiti, it’s very unlikely that cholera will be eliminated from the environment, and we will continue to see surges in cholera case reporting for quite some time.

That’s why PAHO, CDC and UNICEF joined the governments of Haiti and the Dominican Republic in a “call to action” this last January, a plea for the international community, which has pledged so much money, to continue to honor its pledge and put resources toward improving water and sanitation infrastructure in Haiti. Improving this infrastructure will not be easy, and will require a decade or more for Haiti to catch up with its neighbors in the Caribbean and the rest of Latin America.

How has the cholera outbreak in Haiti affected these HIV/TB populations?We’re trying to help the MOH to become a rising star in the Caribbean as a public health institution. It’s a multiyear investment – we started a field epidemiology training program, we’re bolstering laboratory capacity and supporting national disease control programs, including for example, an effort to eliminate lymphatic filariasis from Haiti. Of critical importance is our partnership with PAHO and the government of Haiti to improve the immunization program for children less than five. Haiti has the lowest childhood immunization coverage rates in the western hemisphere. In an effort to quickly turn this around, an immunization catch up campaign for measles, rubella and polio targeting children nine years and younger will be launched in April 2012. Following that, the partnership will strive to improve EPI coverage for all six routine childhood vaccine antigens, and in 2013, will introduce pentavalent, pneumococcal conjugate and rotavirus vaccines.